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Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S Glycoproteins.
Viruses. 2020 09 29; 12(10)V

Abstract

Severe acute respiratory syndrome virus 2 (SARS-CoV-2) is responsible for the current global coronavirus disease 2019 (COVID-19) pandemic, infecting millions of people and causing hundreds of thousands of deaths. The viral entry of SARS-CoV-2 depends on an interaction between the receptor-binding domain of its trimeric spike glycoprotein and the human angiotensin-converting enzyme 2 (ACE2) receptor. A better understanding of the spike/ACE2 interaction is still required to design anti-SARS-CoV-2 therapeutics. Here, we investigated the degree of cooperativity of ACE2 within both the SARS-CoV-2 and the closely related SARS-CoV-1 membrane-bound S glycoproteins. We show that there exist differential inter-protomer conformational transitions between both spike trimers. Interestingly, the SARS-CoV-2 spike exhibits a positive cooperativity for monomeric soluble ACE2 binding when compared to the SARS-CoV-1 spike, which might have more structural restraints. Our findings can be of importance in the development of therapeutics that block the spike/ACE2 interaction.

Authors+Show Affiliations

Centre de Recherche du CHUM, Montréal, QC H2X 0A9, Canada. Department of Microbiology and Immunology, McGill University, Montréal, QC H3A 2B4, Canada.Infectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4712, USA.Centre de Recherche du CHUM, Montréal, QC H2X 0A9, Canada. Departement de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC H2X 0A9, Canada.Centre de Recherche du CHUM, Montréal, QC H2X 0A9, Canada. Departement de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC H2X 0A9, Canada.Centre de Recherche du CHUM, Montréal, QC H2X 0A9, Canada. Departement de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC H2X 0A9, Canada.Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19104, USA.Infectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4712, USA.Centre de Recherche du CHUM, Montréal, QC H2X 0A9, Canada. Department of Microbiology and Immunology, McGill University, Montréal, QC H3A 2B4, Canada. Departement de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC H2X 0A9, Canada.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33003587

Citation

Anand, Sai Priya, et al. "Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S Glycoproteins." Viruses, vol. 12, no. 10, 2020.
Anand SP, Chen Y, Prévost J, et al. Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S Glycoproteins. Viruses. 2020;12(10).
Anand, S. P., Chen, Y., Prévost, J., Gasser, R., Beaudoin-Bussières, G., Abrams, C. F., Pazgier, M., & Finzi, A. (2020). Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S Glycoproteins. Viruses, 12(10). https://doi.org/10.3390/v12101104
Anand SP, et al. Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S Glycoproteins. Viruses. 2020 09 29;12(10) PubMed PMID: 33003587.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interaction of Human ACE2 to Membrane-Bound SARS-CoV-1 and SARS-CoV-2 S Glycoproteins. AU - Anand,Sai Priya, AU - Chen,Yaozong, AU - Prévost,Jérémie, AU - Gasser,Romain, AU - Beaudoin-Bussières,Guillaume, AU - Abrams,Cameron F, AU - Pazgier,Marzena, AU - Finzi,Andrés, Y1 - 2020/09/29/ PY - 2020/09/03/received PY - 2020/09/21/revised PY - 2020/09/24/accepted PY - 2020/10/2/entrez PY - 2020/10/3/pubmed PY - 2020/11/3/medline KW - ACE2-Fc KW - COVID-19 KW - CR3022 antibody KW - Coronavirus KW - SARS-CoV-1 KW - SARS-CoV-2 KW - human ACE2 receptor KW - neutralization KW - spike glycoproteins JF - Viruses JO - Viruses VL - 12 IS - 10 N2 - Severe acute respiratory syndrome virus 2 (SARS-CoV-2) is responsible for the current global coronavirus disease 2019 (COVID-19) pandemic, infecting millions of people and causing hundreds of thousands of deaths. The viral entry of SARS-CoV-2 depends on an interaction between the receptor-binding domain of its trimeric spike glycoprotein and the human angiotensin-converting enzyme 2 (ACE2) receptor. A better understanding of the spike/ACE2 interaction is still required to design anti-SARS-CoV-2 therapeutics. Here, we investigated the degree of cooperativity of ACE2 within both the SARS-CoV-2 and the closely related SARS-CoV-1 membrane-bound S glycoproteins. We show that there exist differential inter-protomer conformational transitions between both spike trimers. Interestingly, the SARS-CoV-2 spike exhibits a positive cooperativity for monomeric soluble ACE2 binding when compared to the SARS-CoV-1 spike, which might have more structural restraints. Our findings can be of importance in the development of therapeutics that block the spike/ACE2 interaction. SN - 1999-4915 UR - https://www.unboundmedicine.com/medline/citation/33003587/Interaction_of_Human_ACE2_to_Membrane_Bound_SARS_CoV_1_and_SARS_CoV_2_S_Glycoproteins_ L2 - https://www.mdpi.com/resolver?pii=v12101104 DB - PRIME DP - Unbound Medicine ER -